EXKIVITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXKIVITY (EXKIVITY).
Irreversible tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, and specifically inhibits EGFR T790M and C797S resistance mutations, with less activity against wild-type EGFR.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP2C8 and CYP2D6. |
| Excretion | Primarily hepatic metabolism with biliary excretion; 91% of total recovered in feces (30% as unchanged drug), <1% in urine. |
| Half-life | Terminal elimination half-life is approximately 48 hours, supporting once-daily dosing for systemic exposure. |
| Protein binding | 99.8% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent Vd is 14.6 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 58-60% under fasted conditions; absorption increased with high-fat meal. |
| Onset of Action | Oral: Time to peak plasma concentration (Tmax) occurs at 4-6 hours post-dose; clinical effect onset not defined. |
| Duration of Action | Duration corresponds to dosing interval (24h) due to half-life; sustained plasma levels achieved with daily dosing. |
150 mg orally once daily with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or dialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): reduce to 100 mg once daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXKIVITY (EXKIVITY).
| Breastfeeding | There are no data on the presence of EXKIVITY in human milk, its effects on the breastfed infant, or its effects on milk production. Due to the potential for serious adverse reactions in breastfed infants (e.g., EGFR inhibition affecting growth and development), advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Based on the mechanism of action (EGFR tyrosine kinase inhibitor) and animal studies, EXKIVITY is predicted to cause fetal harm when administered to a pregnant woman. There are no adequate human data. In animal reproduction studies, embryo-fetal toxicity and teratogenicity (including skeletal abnormalities and reduced fetal weight) occurred at maternal exposures below the human exposure at the recommended dose. Therefore, EXKIVITY is contraindicated in pregnancy. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus. The risk applies throughout all trimesters. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Interstitial lung disease (ILD)/pneumonitis","QTc interval prolongation","Embryo-fetal toxicity","Cutaneous adverse reactions","Diarrhea"] |
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| Fetal Monitoring | If EXKIVITY is inadvertently used during pregnancy, close monitoring of fetal development is recommended, including serial fetal ultrasounds to assess for growth restriction, skeletal anomalies, and amniotic fluid volume. Maternal monitoring should include liver function tests, serum electrolytes, and assessment for adverse events such as diarrhea, rash, and interstitial lung disease. Consider regular pregnancy surveillance by maternal-fetal medicine. |
| Fertility Effects | Based on animal studies and its mechanism of action, EXKIVITY may impair fertility in females. In animal studies, ovarian effects including follicular atresia and reduced corpora lutea were observed, suggesting potential impairment of female fertility. Effects on male fertility have not been adequately studied, but testicular toxicity cannot be excluded. The clinical relevance in humans is unknown. Advise patients of potential impact on reproductive capacity. |